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PMID: 21514219 Published · ppublish English Journal Article Meta-Analysis Research Support, N.I.H., Extramural Review

Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence.

The Lancet. Oncology ·Vol. 12 ·No. 5 ·2011-05-00 ·Pages 477-88

Zhang B, Beeghly-Fadiel A, Long J, Zheng W

Abstract

More than 1000 reports have been published in the past two decades on associations between variants in candidate genes and risk of breast cancer. Results have been generally inconsistent. We did a literature search and meta-analyses to provide a synopsis of the current understanding of the genetic architecture of breast-cancer risk. A systematic literature search for candidate-gene association studies of breast-cancer risk was done in two stages, using PubMed on or before Feb 28, 2010. A total of 24,500 publications were identified, of which 1059 were deemed eligible for inclusion. Meta-analyses were done for 279 genetic variants in 128 candidate genes or chromosomal loci that had at least three data sources. Variants with significant associations by meta-analysis were assessed using the Venice criteria and scored as having strong, moderate, or weak cumulative evidence for an association with breast-cancer risk. 51 variants in 40 genes showed significant associations with breast-cancer risk. Cumulative epidemiological evidence of an association was graded as strong for ten variants in six genes (ATM, CASP8, CHEK2, CTLA4, NBN, and TP53), moderate for four variants in four genes (ATM, CYP19A1, TERT, and XRCC3), and weak for 37 variants. Additionally, in meta-analyses that included a minimum of 10,000 cases and 10,000 controls, convincing evidence of no association with breast-cancer risk was identified for 45 variants in 37 genes. Whereas most genetic variants assessed in previous candidate-gene studies showed no association with breast-cancer risk in meta-analyses, 14 variants in nine genes had moderate to strong evidence for an association. Further evaluation of these variants is warranted. US National Cancer Institute.

MeSH Terms
Antigens, CD/genetics Aromatase/genetics Ataxia Telangiectasia Mutated Proteins Breast Neoplasms/epidemiology,genetics CTLA-4 Antigen Caspase 8/genetics Cell Cycle Proteins/genetics Checkpoint Kinase 2 DNA-Binding Proteins/genetics Evidence-Based Medicine Female Genetic Predisposition to Disease Humans Mutation Nuclear Proteins/genetics Protein Serine-Threonine Kinases/genetics Risk Assessment Risk Factors Telomerase/genetics Tumor Suppressor Protein p53/genetics Tumor Suppressor Proteins/genetics
Chemicals
Antigens, CD CTLA-4 Antigen CTLA4 protein, human Cell Cycle Proteins DNA-Binding Proteins NBN protein, human Nuclear Proteins TP53 protein, human Tumor Suppressor Protein p53 Tumor Suppressor Proteins X-ray repair cross complementing protein 3 Aromatase Checkpoint Kinase 2 ATM protein, human Ataxia Telangiectasia Mutated Proteins CHEK2 protein, human Protein Serine-Threonine Kinases TERT protein, human Telomerase CASP8 protein, human Caspase 8
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Zhang Ben
Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Beeghly-Fadiel Alicia
Long Jirong
Zheng Wei
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Article Info
Journal
The Lancet. Oncology
Abbr.
Lancet Oncol
ISSN
1474-5488
DOI
10.1016/S1470-2045(11)70076-6
Published
2011-05-00
Epub
2011-00-20
Pages
477-88
Language
English
Region
England
NLM ID
100957246
PMCID
PMC3114278
Subset
IM
Grants
NCI NIH HHS · R01 CA148667-02 · United States
NCI NIH HHS · R37 CA070867 · United States
NCI NIH HHS · R01 CA124558-03 · United States
NCI NIH HHS · R01 CA064277 · United States
NCI NIH HHS · R01 CA148667 · United States
NCI NIH HHS · R01 CA124558 · United States
NCI NIH HHS · R37 CA070867-14 · United States
Corrections
CommentIn
PMID: 21514220
External Links
PubMed source DOI: 10.1016/S1470-2045(11)70076-6 PMC Full Text View journal details
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